Abstract

Nitric oxide (NO) has been shown to regulate T cell functions under physiological
conditions, but overproduction of NO may contribute to T lymphocyte dysfunction. NO-dependent
tissue injury has been implicated in a variety of rheumatic diseases, including systemic
lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several studies reported
increased endogenous NO synthesis in both SLE and RA, and recent evidence suggests
that NO contributes to T cell dysfunction in both autoimmune diseases. The depletion
of intracellular glutathione may be a key factor predisposing patients with SLE to
mitochondrial dysfunction, characterized by mitochondrial hyperpolarization, ATP depletion
and predisposition to death by necrosis. Thus, changes in glutathione metabolism may
influence the effect of increased NO production in the pathogenesis of autoimmunity.